Many coronary stenoses are dynamic and are capable of changes in caliber. In the presence of a severe compliant coronary stenosis, even small changes in the area of the stenosis due to physiologic processes or to drugs may importantly affect blood flow through the stenotic artery. In order to understand the factors which affect blood flow through stenotic coronary arteries the mechanisms which control the diameter of normal epicardial coronary arteries must be understood. In this project, these mechanisms will be studied using awake chronically instrumented dogs in which coronary arterial diameter will be measured with sonomicrometry. Little information is presently available concerning control of coronary arterial diameter during exercise. In the proposed project drugs which block specific receptors will be used to study the effects of the sympathetic nervous system on epicardial coronary arterial diameter during exercise. The effects of adenosine and prostaglandins on coronary arterial diameter during exercise will also be studied. Hypertension and hypercholesterolemia affect the vasomotion of arteries. In the proposed project, vasomotion of epicardial coronary arteries at rest and during exercise will be evaluated in dogs with hypertension-induced hypertrophy and in dogs with hypercholesterolemia. In addition, the effects of vasoactive drugs on the hemodynamics of compliant coronary stenoses will be studied in chronically instrumented dogs. This project is planned to contribute to an understanding of the factors controlling the diameter of epicardial coronary arteries and compliant coronary stenoses. These experiments may lead to improved understanding of the pathophysiology of the development of myocardial ischemia and to more rational therapy for ischemic heart disease.